| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Smad3, ALK-5[1]
SIS3 free base specifically targets Smad3, a key downstream signaling molecule in the TGF-β pathway. It inhibits Smad3 phosphorylation without affecting Smad2 phosphorylation, demonstrating high selectivity. |
|---|---|
| ln Vitro |
The connection between Smad3 and Smad4 as well as the phosphorylation of Smad3 caused by TGF-beta1 are reduced by SIS3 free base[1].
SIS3 free base inhibits the myofibroblast differentiation of fibroblasts induced by TGF-β1. It attenuates TGF-β1-induced phosphorylation of Smad3 and the interaction of Smad3 with Smad4. It has no effect on Smad2 phosphorylation, confirming its selectivity for Smad3. |
| ln Vivo |
In vivo activity of SIS3 free base has been demonstrated in preclinical models of fibrosis, cancer, and inflammatory diseases. The compound has shown efficacy in inhibiting Smad3-mediated pathological processes in various disease models.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for SIS3 free base typically involve cell-free kinase activity assays using purified Smad3 protein or cellular lysates. The compound is incubated with Smad3 in the presence of ATP and TGF-β receptor kinase, and Smad3 phosphorylation is measured using phospho-specific antibodies in Western blot or ELISA-based assays.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: Human dermal fibroblasts Tested Concentrations: 0.3, 1, 3, 10 μM Incubation Duration:For 1 hour Experimental Results: Attenuated the TGF-beta1-induced phosphorylation of Smad3 and interaction of Smad3 with Smad4. For in vitro cellular experiments, SIS3 free base is dissolved in DMSO and diluted in cell culture medium. Fibroblasts or other cell types are treated with the compound at concentrations ranging from 1-20 μM in the presence of TGF-β1 stimulation. Smad3 and Smad2 phosphorylation are assessed by Western blot using phospho-specific antibodies. Myofibroblast differentiation is evaluated by measuring α-SMA expression and collagen production. Cell proliferation and migration assays can also be performed. |
| Animal Protocol |
For in vivo animal experiments, SIS3 free base is formulated in suitable vehicles such as PBS, carboxymethyl cellulose, or PEG400 for administration to mouse or rat models. The compound may be administered orally, intraperitoneally, or subcutaneously. Pharmacodynamic endpoints include assessment of Smad3 phosphorylation in target tissues, evaluation of fibrosis markers (collagen, α-SMA), measurement of inflammatory cytokine levels, and assessment of tumor growth in cancer models.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SIS3 free base have not been extensively characterized. Standard PK studies would assess parameters such as half-life, oral bioavailability, clearance, and tissue distribution in rodent models following oral or intravenous administration.
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| Toxicity/Toxicokinetics |
Toxicological data for SIS3 free base is limited to preclinical research settings. The compound is intended for laboratory use only and has not been evaluated for human therapeutic safety. Standard safety precautions should be observed during handling.
|
| References | |
| Additional Infomation |
SIS3 free base is an enamide formed by the condensation of the amino group of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline with the carboxyl group of (2E)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid. It is a Smad3 inhibitor. SIS3 belongs to the isoquinolines, pyrrolopyridines, monocarboxylic acid amides, aromatic ethers, enamides, and tertiary amides. It is the conjugate base of the SIS3 free base (1+).
SIS3 free base is a potent and specific inhibitor of Smad3 phosphorylation. It is widely used in preclinical research to explore pathological mechanisms in fibrosis, cancer, and inflammatory diseases, supporting the development of therapeutic strategies targeting TGF-β/SMAD3 signaling pathways. No clinical trials or regulatory approvals have been reported. |
| Molecular Formula |
C28H27N3O3
|
|---|---|
| Molecular Weight |
453.53
|
| Exact Mass |
453.205
|
| CAS # |
521985-36-4
|
| Related CAS # |
SIS3;521984-48-5
|
| PubChem CID |
10138988
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.21±0.1 g/cm3(Predicted)
|
| Boiling Point |
721.8±60.0 °C(Predicted)
|
| LogP |
4.3
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
34
|
| Complexity |
724
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C(=C(C2=C1N=CC=C2)/C=C/C(=O)N3CCC4=CC(=C(C=C4C3)OC)OC)C5=CC=CC=C5
|
| InChi Key |
IJYPHMXWKKKHGT-VAWYXSNFSA-N
|
| InChi Code |
InChI=1S/C28H27N3O3/c1-30-27(19-8-5-4-6-9-19)22(23-10-7-14-29-28(23)30)11-12-26(32)31-15-13-20-16-24(33-2)25(34-3)17-21(20)18-31/h4-12,14,16-17H,13,15,18H2,1-3H3/b12-11+
|
| Chemical Name |
(E)-1-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-3-(1-methyl-2-phenylpyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (220.49 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2049 mL | 11.0246 mL | 22.0493 mL | |
| 5 mM | 0.4410 mL | 2.2049 mL | 4.4099 mL | |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.2049 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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